BACKGROUND: The metabolic or proliferative abnormalities that are characteristic of tumor cells can lead to abnormal fibrinolysis or coagulation system activity, with certain tumors exhibiting hypercoagulability or existing in a fibrinolytic state. However, the utility of biomarkers of coagulation and fibrinolysis when seeking to differentiate between benign gallbladder disease and malignant gallbladder tumors remains uncertain. METHODS: This study included a total of 81 patients with benign gallbladder polyps and 94 patients with malignant gallbladder tumors. Pre-biopsy or pretreatment levels of PT, APTT, FIB, D-dimer, FDP, PLT, PIC, TAT, TM, and t-PAIC from these patients were compared using Mann-Whitney tests. The baseline data of the patients were analyzed using chi-square tests, and the diagnostic utility of these biomarkers in distinguishing between benign and malignant gallbladder lesions was evaluated using ROC curves, and Spearman correlation analysis was employed to assess the correlation between these indicators and tumor parameters. RESULTS: The average age of malignant gallbladder tumor group was higher than benign gallbladder polyp group. And the base line analysis showed that there was a statistic difference in age, history of smoking, drinking, biliary tract disease, BMI of over weight between these two groups. In patients with malignant gallbladder tumors, FIB, D-dimer, FDP, PIC, TAT, TM, and t-PAIC levels were significantly elevated relative to those in patients affected by benign gallbladder polyp. The AUC for FIB, D-dimer, and FDP was 0.8469, 0.6514, 0.5950, while for PIC, TAT, TM, t-PAIC and four biomarker combined diagnosed was 0.8455, 0.6554, 0.7130, 0.6806, and 0.8859. Among these, TM was associated with the vascular invasion of tumor patients; TAT and t-PAIC were associated with neural invasion; D-dimer and FDP were related to the maximum tumor diameter; and FDP had a certain correlation with the tumor stage. CONCLUSIONS: In gallbladder tumor patients, conventional coagulation metrics like FIB, D-dimer, and FDP, as well as newer thrombotic indicators such as PIC, TAT, TM, and t-PAIC, were obviously increased. Correlations with tumor parameters suggested their potential as biomarkers to distinguish benign from malignant gallbladder growths.
BACKGROUND: Antibiotic-associated diarrhea (AAD) refers to symptoms of diarrhea that cannot be explained by other causes after the use of antibiotics. AAD is thought to be caused by a disruption of intestinal ecology due to antibiotics. Fecal Microbiota Transplantation (FMT) is a treatment method that involves transferring microbial communities from the feces of healthy individuals into the patient's gut. METHOD: We selected 23 AAD patients who received FMT treatment in our department. Before FMT, we documented patients' bowel movement frequency, abdominal symptoms, routine blood tests, and inflammatory markers, and collected fecal samples for 16S rRNA sequencing to observe changes in the intestinal microbiota. Patients' treatment outcomes were followed up 1 month and 3 months after FMT. RESULTS: Out of the 23 AAD patients, 19 showed a clinical response to FMT with alleviation of abdominal symptoms. Among them, 82.61% (19/23) experienced relief from diarrhea, 65% (13/20) from abdominal pain, 77.78% (14/18) from abdominal distension, and 57.14% (4/7) from bloody stools within 1 month after FMT. Inflammatory markers IL-8 and CRP significantly decreased after FMT, but there were no noticeable changes in WBC, IL-6, and TNF-α before and after transplantation. After FMT, the abundance of Bacteroides and Faecalibacterium increased in patients' fecal samples, while the abundance of Escherichia-Shigella and Veillonella decreased. CONCLUSION: FMT has a certain therapeutic effect on AAD, and can alleviate abdominal symptoms and change the intestinal microbiota of patients.
Anti-Bacterial Agents , Diarrhea , Fecal Microbiota Transplantation , Feces , Gastrointestinal Microbiome , RNA, Ribosomal, 16S , Humans , Diarrhea/microbiology , Diarrhea/therapy , Fecal Microbiota Transplantation/methods , Female , Male , Middle Aged , Anti-Bacterial Agents/adverse effects , Feces/microbiology , Adult , RNA, Ribosomal, 16S/genetics , Aged , Treatment Outcome , Bacteria/classification , Bacteria/isolation & purification , Bacteria/genetics
BACKGROUND: Patients with dysplasia of the hip (DDH) have different degrees of bone defects above and outside the acetabulum, and anatomically reconstructing the acetabular centre of rotation is difficult in primary total hip arthroplasty (THA). METHODS: From April 2012 to December 2022, 64 patients (64 hips) with DDH treated with THA with structural bone graft in the superolateral acetabulum were selected. The Oxford hip score(OHS), Barthel index (BI), leg length discrepancy, Wibegr central edge-angle(CE), gluteus medius muscle strength, vertical and horizontal distance of the hip rotation center, coverage rate of the bone graft and complications were used to evaluate the clinical effectiveness of the patients. RESULTS: All patients were followed up for an average of 7.3±1.9 years. The OHS improved significantly after the operation (P<0.001). The postoperative BI was significantly greater than that before operation (P<0.001). The postoperative leg length discrepancy was significantly lower than that before the operation (P<0.001). Postoperative bedside photography revealed that the height and horizontal distance to the hip rotation center were significantly lower after surgery than before surgery (P<0.001). The postoperative CE was significantly greater than that before surgery (P<0.001). No acetabular component loosening or bone graft resorption was found during the postoperative imaging examination. CONCLUSIONS: The use of biological acetabular cup combined with structural bone graft in the superolateral acetabulum in THA for DDH can obtain satisfactory medium and long-term clinical and radiological results.
CD52 is an important functional regulator involved in the development of human cancer. In this study, the clinical significance and biological function of CD52 in the malignant behavior of non-small cell lung cancer (NSCLC) were explored. In this study, immunohistochemical (IHC) staining was performed to determine the expression pattern of CD52 in NSCLC. Loss of function assays were used to evaluate the biological functions of CD52 in NSCLC cells in vitro and in vivo. Our data indicated that the expression of CD52 was significantly elevated in NSCLC and correlated with the patient prognosis. Functionally, downregulation of CD52 expression significantly suppressed the proliferation, migration, aerobic glycolysis and tumorigenesis of NSCLC cells. Moreover, CD52 regulated aerobic glycolysis of NSCLC cells through the AKT pathway. Furthermore, aerobic glycolysis induced by 2-DG inhibited the proliferation of NSCLC cells. In conclusion, CD52 knockdown inhibited aerobic glycolysis and malignant behavior of NSCLC cells through AKT signaling pathway, which may be employed in an alternative therapeutic target for NSCLC.
In recent years, Heated tobacco products (HTP) have gradually entered the market and become more and more popular with consumers because of their low risk (compared with traditional cigarette). With the increasing popularity and proportion of HTP in the international market, people pay more and more attention to the safety evaluation of HTP, but there is still a lack of systematic review of HTP safety research. In this review, the harmful components of HTP, multi-organ functional programming effects (including respiratory system, cardiovascular system, etc.), and mechanism of the effect generation (including oxidative stress, inflammatory response, etc.) were systematically reviewed, the safety effects of HTP and traditional cigarettes were compared in detail, and the shortcomings and future research directions in the field of HTP safety were discussed. In summary, this review conforms to the general trend of contemporary "tobacco and health", helps people to understand and evaluate HTP more systematically, and provides a strong theoretical support and literature basis for the tobacco industry to carry out HTP risk assessment and exposure improvement.
Hot Temperature , Tobacco Products , Animals , Humans , Consumer Product Safety , Hot Temperature/adverse effects , Risk Assessment , Tobacco Products/adverse effects
OBJECTIVE: To examine the effects of web neonatal intensive care unit diaries on the mental health, quality of life, sleep quality, care ability, and hormone levels of parents of preterm infants in the neonatal intensive care unit. DESIGN: Prospective randomized controlled parallel-group clinical trial. SETTING: Maternal and Child Health Hospital, Fujian, China. METHODS: The control group received routine neonatal intensive care unit care, while the intervention group received a web neonatal intensive care unit diary based on routine care. Outcomes, including anxiety, depression, and post-traumatic stress disorder symptoms, quality of life, sleep quality, care ability, and cortisol and melatonin levels, were evaluated at T1 (Time 1, before the intervention), T2 (Time 2, immediately after the intervention), and T3 (Time 3, 1 month after the intervention). RESULTS: Seventy pairs of parents of preterm infants in the neonatal intensive care unit were randomly allocated to two groups: intervention (n = 35) and control (n = 35). The anxiety scores in the intervention group were significantly lower at T2 and T3 than those in the control group (P < 0.001). The care ability scores in the intervention group were significantly higher at T2 and T3 (P < 0.001). The prevalence of post-traumatic stress disorder at T3 was significantly different between the groups (P = 0.040). No significant differences were observed in the quality of life or sleep quality between the groups at T2 and T3 (P > 0.05). No significant differences were observed in cortisol and melatonin levels between the groups (P > 0.05). CONCLUSIONS: Web neonatal intensive care unit diaries effectively relieved anxiety symptoms, reduced the prevalence of post-traumatic stress disorder, and enhanced the care abilities of parents of preterm infants in the neonatal intensive care unit. IMPLICATIONS FOR CLINICAL PRACTICE: Web neonatal intensive care unit diary can be considered in clinical practice as a convenient psychological intervention method, especially among parents of preterm infants in the neonatal intensive care unit.
Type 17 helper T cells (Th17)-dominant neutrophilic airway inflammation is critical in the pathogenesis of steroid-resistant airway inflammation such as severe asthma. Small extracellular vesicles (sEV) derived from human mesenchymal stem cells (MSCs) display extensive therapeutic effects and advantages in many diseases. However, the role of MSC-sEV in Th17-dominant neutrophilic airway inflammation and the related mechanisms are still poorly studied. Here we found that MSC-sEV significantly alleviated the infiltration of inflammatory cells in peribronchial interstitial tissues and reduced levels of inflammatory cells, especially neutrophils, in bronchoalveolar lavage fluids (BALF) of mice with neutrophilic airway inflammation. Consistently, MSC-sEV significantly decreased levels of IL-17A in BALF and Th17 in lung tissues. Furthermore, we found that labelled MSC-sEV were taken up by human CD4+ T cells most obviously at 12 h after incubation, and distributed mostly in mouse lungs. More importantly, potential signaling pathways involved in the MSC-sEV mediated inhibition of Th17 polarization were found using RNA sequencing. Using Western blot, JAK2-STAT3 pathway was identified as an important role in the inhibition of Th17 polarization by MSC-sEV. We found that proteins in MSC-sEV were mostly involved in the therapeutic effects of MSC-sEV. In total, our study suggested that MSC-sEV could be a potential therapeutic strategy for the treatment of neutrophilic airway inflammation.
Extracellular Vesicles , Mesenchymal Stem Cells , Neutrophils , STAT3 Transcription Factor , Th17 Cells , Th17 Cells/immunology , Humans , Animals , Extracellular Vesicles/metabolism , Extracellular Vesicles/immunology , Mesenchymal Stem Cells/immunology , Mesenchymal Stem Cells/metabolism , Mice , Neutrophils/immunology , STAT3 Transcription Factor/metabolism , Janus Kinase 2/metabolism , Interleukin-17/metabolism , Lung/immunology , Lung/pathology , Mice, Inbred C57BL , Cells, Cultured , Bronchoalveolar Lavage Fluid/immunology , Bronchoalveolar Lavage Fluid/cytology , Asthma/immunology , Asthma/therapy , Male , Signal Transduction , Female , Disease Models, Animal
Use of magnetic resonance (MR) imaging in radiation therapy has increased substantially in recent years as more radiotherapy centers are having MR simulators installed, requesting more time on clinical diagnostic MR systems, or even treating with combination MR linear accelerator (MR-linac) systems. With this increased use, to ensure the most accurate integration of images into radiotherapy (RT), RT immobilization devices and accessories must be able to be used safely in the MR environment and produce minimal perturbations. The determination of the safety profile and considerations often falls to the medical physicist or other support staff members who at a minimum should be a Level 2 personnel as per the ACR. The purpose of this guidance document will be to help guide the user in making determinations on MR Safety labeling (i.e., MR Safe, Conditional, or Unsafe) including standard testing, and verification of image quality, when using RT immobilization devices and accessories in an MR environment.
Immobilization , Magnetic Resonance Imaging , Magnetic Resonance Imaging/instrumentation , Humans , Immobilization/instrumentation , Radiotherapy, Image-Guided/instrumentation
Illustrating the biodegradation processes of multi-component volatile organic compounds (VOCs) will expedite the implication of biotechnology in purifying industrial exhaust. Here, performance shifts of microbial fuel cell and biotrickling filter combined system (MFC-BTF) are investigated for removing single and dual components of toluene and benzene. Synchronous removal of toluene (95 %) and benzene (97 %) are achieved by MFC-BTF accompanied with the output current of 0.41 mA. Elevated content of extracellular polymeric substance facilitates the mass transfer of benzene with the presence of toluene. Strains of Bacteroidota, Proteobacteria and Chloroflexi contribute to the removal of dual components VOCs. Empty bed reaction time and the VOCs concentration are the important factors influencing their dissolution in the system. The biodegradation of toluene and benzene proceeds with 2-hydroxymuconic semialdehyde and o-hydroxybenzoic acid as the main intermediates. These results provide a comprehensive understanding of multi-component VOCs removal by MFC-BTF and guide the system design, optimization, and scale-up.
Benzene , Biodegradation, Environmental , Bioelectric Energy Sources , Toluene , Toluene/metabolism , Benzene/metabolism , Filtration/methods , Volatile Organic Compounds/metabolism , Gases/metabolism
BACKGROUND: Small renal masses (SRMs) have been shown to have low malignant potential. Active surveillance (AS), typically characterized by regular follow-up and delayed nephrectomy if necessary, is recommended as an option for frail patients with SRMs. Nevertheless, the impact of tumor size on survival in T1a RCC patients undergoing delayed nephrectomy for SRMs remains unclear. METHODS: Patients diagnosed with non-metastatic T1a RCC who underwent nephrectomy were identified from the Surveillance, Epidemiology, and End Results (SEER) database and divided into immediate (< 6 months) and delayed nephrectomy (≥ 6 months) groups based on the duration from diagnosis to nephrectomy. After propensity score matching (PSM), overall survival (OS) and cancer-specific survival (CSS) were estimated by K-M curves and compared with log-rank test. RESULTS: A total of 27,502 patients were enrolled, of whom 26,915 (97.9%) received immediate nephrectomy and 587 (2.1%) received delayed nephrectomy. After PSM, 1174 patients who underwent immediate nephrectomy and 587 patients who underwent delayed nephrectomy were included. With a median delay of 7 months, delayed nephrectomy resulted in non-inferior OS for RCC tumors sized 0.1-2.0 cm (HR = 1.12, p = 0.636). However, for RCC tumors sized 2.1-3.0 cm (HR = 1.60, p = 0.008) and 3.1-4.0 cm (HR = 1.89, p < 0.001), delayed nephrectomy showed inferior OS compared to immediate nephrectomy. Delayed nephrectomy did not result in significantly worse CSS than immediate nephrectomy in all tumor size subgroups (all p > 0.05), however this may be due to sample size limiting statistical power. CONCLUSION: Based on the SEER database, we found that with a median delay of 7 months, 2 cm may be an appropriate cut-off point of delayed nephrectomy for patients diagnosed with non-metastatic T1a RCC.
BACKGROUND: As the internet develops and 5G technology becomes increasingly prominent, the internet has become a major source of health-related information. Increasingly, people use the internet to find health-related information, and digital health literacy is now a set of essential capabilities to improve their health in the digital era. However, little is known about the factors that influencing digital health literacy. This study aimed to assess digital health literacy scores and identify its influencing factors among internet users in China. Additionally, this study explored the participant's actual skills using an additional set of performance-based items from the Digital Health Literacy Instrument (DHLI). METHODS: An online cross-sectional study was conducted in August 2022. Participants aged ≥18 years were recruited to complete the survey. Data were collected using the Chinese revised version of the DHLI, the self-reported internet use questionnaire, and the sociodemographic questionnaire. We conducted multivariate linear regression analyses to explore the relationships among the sociodemographic variables, behavior of internet use, and the digital health literacy scores. RESULTS: In total, 702 participants completed the survey. The mean DHLI score was 2.69 ± 0.61. Multivariate linear regression analyses showed that the age groups 35-49 (ß = - 0.08, P = 0.033), 50-64 (ß = - 0.161, P < 0.001), and ≥ 65 (ß = - 0.138, P < 0.001) were negatively associated with DHL scores. However, education level, including bachelor's or associate degree (ß = 0.255, P = 0.002) and master's degree and above (ß = 0.256, P < 0.001), frequency of health-related Internet usage (ß = 0.192, P < 0.001), the number of digital devices used (ß = 0.129, P = 0.001), and OHISB (ß = 0.103, P = 0.006) showed a positive relationship with DHL scores. CONCLUSIONS: The study findings demonstrate that age, educational levels, number of technological devices used, and greater use of the web for health information were independently associated with DHL scores. Healthcare providers should consider providing training programs tailored to specific sociodemographic factors to improve the ability that find and use accurate information online to meet digital health services, which contributes to enhance their self-management and reduce health disparities.
Health Literacy , Telemedicine , Humans , Adolescent , Adult , Digital Health , Cross-Sectional Studies , Surveys and Questionnaires , Internet , China
The Chinese soft-shelled turtle (Pelodiscus sinensis) is an important freshwater aquaculture turtle due to its taste and nutritional and medicinal value. More ecological culturing modes, such as rice-turtle co-culture, should be developed to meet the ecological benefit demand. We compared growth, physiological parameters, and transcriptome data to detect the physiological responses and regulatory mechanisms of pond-cultured turtles as compared to co-cultured turtles. The co-cultured turtles grew slower than pond-cultured turtles. The gonadosomatic index of co-cultured male turtles was lower than that of pond-cultured male turtles, and both the mesenteric fat index and limb fat index were lower in co-cultured turtles than in pond-cultured turtles (p < 0.05). The blood GLU of the co-cultured turtles was significantly lower than the GLU of the pond-cultured turtles (p < 0.05), while the values of CRE, UA, BUN, AKP, ACP, GOT, and CAT were higher in the co-cultured turtles than in the pond-cultured turtles (p < 0.05). In total, 246 and 598 differentially expressed genes (DEGs) were identified in the brain and gut from turtles cultured in the two different modes, respectively. More DEGs were related to environmental information processing, metabolism, and human diseases. In the brain, the top enriched pathways of DEGs included the longevity regulating pathway, glycerolipid metabolism, cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, and PI3K-Akt signaling pathway, while in the gut, the top enriched pathways of DEGs included the cell cycle, DNA replication, cellular senescence, and p53 signaling pathway. The turtles acclimated to the different culturing conditions by adjusting their growth, physiological, and biochemical characteristics and related gene expression during a short culture period.
BACKGROUND: Partial splenic embolization (PSE) has been suggested as an alternative to splenectomy in the treatment of hypersplenism. However, some patients may experience recurrence of hypersplenism after PSE and require splenectomy. Currently, there is a lack of evidence-based medical support regarding whether preoperative PSE followed by splenectomy can reduce the incidence of complications. AIM: To investigate the safety and therapeutic efficacy of preoperative PSE followed by splenectomy in patients with cirrhosis and hypersplenism. METHODS: Between January 2010 and December 2021, 321 consecutive patients with cirrhosis and hypersplenism underwent splenectomy at our department. Based on whether PSE was performed prior to splenectomy, the patients were divided into two groups: PSE group (n = 40) and non-PSE group (n = 281). Patient characteristics, postoperative complications, and follow-up data were compared between groups. Propensity score matching (PSM) was conducted, and univariable and multivariable analyses were used to establish a nomogram predictive model for intraoperative bleeding (IB). The receiver operating characteristic curve, Hosmer-Lemeshow goodness-of-fit test, and decision curve analysis (DCA) were employed to evaluate the differentiation, calibration, and clinical performance of the model. RESULTS: After PSM, the non-PSE group showed significant reductions in hospital stay, intraoperative blood loss, and operation time (all P = 0.00). Multivariate analysis revealed that spleen length, portal vein diameter, splenic vein diameter, and history of PSE were independent predictive factors for IB. A nomogram predictive model of IB was constructed, and DCA demonstrated the clinical utility of this model. Both groups exhibited similar results in terms of overall survival during the follow-up period. CONCLUSION: Preoperative PSE followed by splenectomy may increase the incidence of IB and a nomogram-based prediction model can predict the occurrence of IB.
Bilateral diffuse metastatic lung adenocarcinoma (BLDM-LUAD) is a special imaging pattern of lung adenocarcinoma (LUAD). We retrospectively assessed survival outcomes and co-mutation characteristics of BLDM-LUAD patients harboring epidermal growth factor receptor (EGFR) mutations who were treated with EGFR-yrosine kinase inhibitors (TKIs). From May 2016 to May 2021, among 458 patients who submitted samples for next generation sequencing (NGS) detection in 1125 patients with non-small-cell lung cancer (NSCLC), and 44 patients were diagnosed as BLDM-LUAD. In order to analyze the survival outcomes of BLDM-LUAD patients harboring EGFR mutations who were treated with EGFR-TKIs, the factors age, gender, smoking history, hydrothorax, site of EGFR mutations and EGFR-TKIs treatment were adjusted using propensity score-matching (PSM). The Kaplan-Meier survival curves and log-rank test were used to analyze progression-free survival (PFS) and overall survival (OS). The co-mutation characteristics of BLDM-LUAD patients harboring EGFR mutations were analyzed by NGS panels. 64 patients with advanced lung adenocarcinoma harboring EGFR mutations and first-line treatment of EGFR-TKIs were successfully matched. BLDM-LUAD (n = 32) have significantly longer median PFS than control group (n = 32) (mPFS: 14 vs 6.2 months; p = .002) and insignificantly longer median OS than control group (mOS: 45 vs 25 months; p = .052). The patients with BLDM-LUAD have the higher frequency of EGFR mutation than control group (84.1% vs 62.0%) before PSM. The co-mutation genes kirsten rat sarcoma viral oncogene homolog (KRAS) (9.4%), ataxia telangiectasia-mutated (ATM) (7.4%) and mesenchymal-epithelial transition (MET) (3.1%) only appeared in the control group after PSM. The BLDM-LUAD harboring EGFR mutations was associated with a favorable prognosis to EGFR-TKI.
Adenocarcinoma of Lung , Carcinoma, Non-Small-Cell Lung , ErbB Receptors , Lung Neoplasms , Humans , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , ErbB Receptors/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Mutation , Prognosis , Protein Kinase Inhibitors/therapeutic use , Retrospective Studies
Patients with concurrent intrahepatic cholangiocarcinoma (ICC) and hepatolithiasis generally have poor prognoses. Hepatolithiasis is once considered the primary cause of ICC, although recent insights indicate that bacteria in the occurrence of hepatolithiasis can promote the progression of ICC. By constructing in vitro and in vivo ICC models and patient-derived organoids (PDOs), it is shown that Escherichia coli induces the production of a novel RNA, circGLIS3 (cGLIS3), which promotes tumor growth. cGLIS3 binds to hnRNPA1 and G3BP1, resulting in the assembly of stress granules (SGs) and suppression of hnRNPA1 and G3BP1 ubiquitination. Consequently, the IKKα mRNA is blocked in SGs, decreasing the production of IKKα and activating the NF-κB pathway, which finally results in chemoresistance and produces metastatic phenotypes of ICC. This study shows that a combination of Icaritin (ICA) and gemcitabine plus cisplatin (GP) chemotherapy can be a promising treatment strategy for ICC.
Bile Duct Neoplasms , Cholangiocarcinoma , Disease Progression , Escherichia coli , NF-kappa B , Stress Granules , Animals , Humans , Mice , Bile Duct Neoplasms/metabolism , Bile Duct Neoplasms/genetics , Bile Duct Neoplasms/pathology , Cholangiocarcinoma/metabolism , Cholangiocarcinoma/genetics , Cholangiocarcinoma/pathology , Disease Models, Animal , DNA Helicases , Escherichia coli/genetics , Escherichia coli/metabolism , Gemcitabine , NF-kappa B/metabolism , NF-kappa B/genetics , Poly-ADP-Ribose Binding Proteins/metabolism , Poly-ADP-Ribose Binding Proteins/genetics , RNA Helicases , RNA Recognition Motif Proteins/metabolism , RNA Recognition Motif Proteins/genetics , Signal Transduction/genetics , Stress Granules/metabolism , Stress Granules/genetics
Noncompressible hemorrhage is a leading cause of preventable death in battlefield/civilian trauma. The development of novel injectable and biodegradable hemostatic sponges, with rapid shape recovery and excellent antibacterial activity that can control hemorrhage in noncompressible bleeding sites and promote in situ tissue regeneration is still urgently needed. In this study, thermo/pH sensitive 2-hydroxypropyl-trimethylammonium chitins (QCHs) with low degree of quaternization substitution (DS: 0.07-0.23) and high degree of acetylation (DA: 0.91-0.94) were synthesized homogeneously for the first time. Their chemical compositions including DS and DA were characterized accurately by proton NMR for the first time. High strength QCH based sponges with good water/blood absorbency, rapid shape recovery and good antibacterial activity were prepared without using any crosslinkers but only due to their thermosensitive property, since they are soluble at low temperature but insoluble at high temperature. Compared with commercial products, the QCH sponges with cationic groups had the stronger pro-coagulant ability, better hemostatic effect in normal/heparinized liver perforation and femoral artery models in rats and porcine subclavian arteriovenous resection model. Moreover, the porous structure and biodegradability of the QCH sponges could promote in situ tissue regeneration. Overall, the QCH sponges show great clinical translational potential for noncompressible hemorrhage and tissue regeneration.
Chitin , Hemostatics , Rats , Animals , Swine , Chitin/chemistry , Hemostasis , Hemostatics/pharmacology , Hemorrhage/drug therapy , Anti-Bacterial Agents/pharmacology
Alzheimer's disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia in elderly people and substantially affects patient quality of life. Oxidative stress is considered a key factor in the development of AD. Nrf2 plays a vital role in maintaining redox homeostasis and regulating neuroinflammatory responses in AD. Previous studies show that potassium 2-(1-hydroxypentyl)-benzoate (PHPB) exerts neuroprotective effects against cognitive impairment in a variety of dementia animal models such as APP/PS1 transgenic mice. In this study we investigated whether PHPB ameriorated the progression of AD by reducing oxidative stress (OS) damage. Both 5- and 13-month-old APP/PS1 mice were administered PHPB (100 mg·kg-1·d-1, i.g.) for 10 weeks. After the cognition assessment, the mice were euthanized, and the left hemisphere of the brain was harvested for analyses. We showed that 5-month-old APP/PS1 mice already exhibited impaired performance in the step-down test, and knockdown of Nrf2 gene only slightly increased the impairment, while knockdown of Nrf2 gene in 13-month-old APP/PS1 mice resulted in greatly worse performance. PHPB administration significantly ameliorated the cognition impairments and enhanced antioxidative capacity in APP/PS1 mice. In addition, PHPB administration significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the expression levels of Nrf2, HO-1 and NQO-1 in APP/PS1 mice, but these changes were abolished by knockdown of Nrf2 gene. In SK-N-SH APPwt cells and primary mouse neurons, PHPB (10 µM) significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the level of Nrf2, which were blocked by knockdown of Nrf2 gene. In summary, this study demonstrates that PHPB exerts a protective effect via the Akt/GSK3ß/Nrf2 pathway and it might be a promising neuroprotective agent for the treatment of AD.
Alzheimer Disease , Disease Models, Animal , Memory Disorders , Mice, Transgenic , NF-E2-Related Factor 2 , Oxidative Stress , Signal Transduction , Animals , NF-E2-Related Factor 2/metabolism , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Oxidative Stress/drug effects , Signal Transduction/drug effects , Mice , Memory Disorders/drug therapy , Memory Disorders/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Male , Humans , Mice, Inbred C57BL
Fine root (diameter < 2 mm) distribution influences the potential for resource acquisition in soil profiles, which defines how plants interact with local soil environments; however, a deep understanding of how fine root vertical distribution varies with soil structural variations and across growth years is lacking. We subjected four xerophytic species native to an arid valley of China, Artemisia vestita, Bauhinia brachycarpa, Sophora davidii, and Cotinus szechuanensis, to increasing rock fragment content (RFC) treatments (0%, 25%, 50%, and 75%, v v-1) in an arid environment and measured fine root vertical profiles over 4 years of growth. Fine root depth and biomass of woody species increased with increasing RFC, but the extent of increase declined with growth years. Increasing RFC also increased the degree of interannual decreases in fine root diameter. The limited supply of soil resources in coarse soils explained the increases in rooting depth and variations in the pattern of fine root profiles across RFC. Fine root depth and biomass of the non-woody species (A. vestita) in soil profiles decreased with the increase in RFC and growth years, showing an opposite pattern from the other three woody species. Within woody species, the annual increase in fine root biomass varied with RFC, which led to large interannual differences in the patterns of fine root profiles. Younger or non-woody plants were more susceptible to soil environmental changes than the older or woody plants. These results reveal the limitations of dry and rocky environments on the growth of different plants, with woody and non-woody plants adjusting their root vertical distribution through opposite pathways to cope with resource constraints, which has management implications for degraded agroforest ecosystems.
The fusion genes NRG1 and NRG2 , members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1 -positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2 . Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.
